WNT16

Summary

WNT16 (Wnt family member 16, HGNC:16267) is a protein-coding gene on chromosome 7q31.31, encoding Protein Wnt-16 (Q9UBV4). Ligand for members of the frizzled family of seven transmembrane receptors.

The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It contains two transcript variants diverging at the 5’ termini. These two variants are proposed to be the products of separate promoters and not to be splice variants from a single promoter. They are differentially expressed in normal tissues, one of which (variant 2) is expressed at significant levels only in the pancreas, whereas another one (variant 1) is expressed more ubiquitously with highest levels in adult kidney, placenta, brain, heart, and spleen.

Source: NCBI Gene 51384 — RefSeq curated summary.

At a glance

• GWAS associations: 51
• Clinical variants (ClinVar): 58 total
• MANE Select transcript: NM_057168

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16267
Approved symbol	WNT16
Name	Wnt family member 16
Location	7q31.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000002745
Ensembl biotype	protein_coding
OMIM	606267
Entrez	51384

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000222462, ENST00000361301

RefSeq mRNA: 2 — MANE Select: NM_057168 NM_016087, NM_057168

CCDS: CCDS5780, CCDS5781

Canonical transcript exons

ENST00000222462 — 4 exons

Exon	Start	End
ENSE00000719279	121331678	121331964
ENSE00001018742	121329000	121329387
ENSE00001841941	121338881	121341104
ENSE00002531493	121329567	121329817

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 97.57.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0791 / max 501.1863, expressed in 189 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80812	1.0133	180
80813	0.0433	12
80814	0.0153	8
204674	0.0072	2

Top tissues by expression

265 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	97.57	gold quality
skin of hip	UBERON:0001554	83.49	gold quality
upper leg skin	UBERON:0004262	79.43	gold quality
skin of abdomen	UBERON:0001416	74.53	gold quality
zone of skin	UBERON:0000014	73.82	gold quality
skin of leg	UBERON:0001511	73.17	gold quality
calcaneal tendon	UBERON:0003701	68.85	gold quality
granulocyte	CL:0000094	66.43	gold quality
vagina	UBERON:0000996	65.98	gold quality
cauda epididymis	UBERON:0004360	65.79	gold quality
germinal epithelium of ovary	UBERON:0001304	64.50	silver quality
endothelial cell	CL:0000115	64.48	silver quality
tendon	UBERON:0000043	63.38	gold quality
ventricular zone	UBERON:0003053	62.94	gold quality
prefrontal cortex	UBERON:0000451	60.29	gold quality
upper arm skin	UBERON:0004263	59.79	gold quality
cervix epithelium	UBERON:0004801	58.26	gold quality
ectocervix	UBERON:0012249	58.23	gold quality
lymph node	UBERON:0000029	58.04	gold quality
uterine cervix	UBERON:0000002	57.73	gold quality
anterior cingulate cortex	UBERON:0009835	56.94	gold quality
cingulate cortex	UBERON:0003027	56.91	gold quality
spleen	UBERON:0002106	55.86	gold quality
cartilage tissue	UBERON:0002418	55.70	gold quality
penis	UBERON:0000989	55.40	gold quality
pancreatic ductal cell	CL:0002079	54.51	silver quality
urethra	UBERON:0000057	54.37	gold quality
colonic epithelium	UBERON:0000397	53.94	gold quality
islet of Langerhans	UBERON:0000006	53.63	gold quality
tendon of biceps brachii	UBERON:0008188	53.63	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.54

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1, JUN, PBX1, TCF3

miRNA regulators (miRDB)

79 targeting WNT16, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-8087	99.90	69.55	1351

Literature-anchored findings (GeneRIF, showing 35)

• genomic analysis of conserved sequences between human, rat, and zebrafish WNT16 (PMID:15756456)
• Targeted-Wnt16b inhibition leads to apoptotic cell death, and Wnt16b mediates its effect through canonical Wnt pathway involving dishevelled-2, beta-catenin and survivin; Wnt16 plays an important role in leukemogenesis. (PMID:16007226)
• Targeted-E2A-PBX1 inhibition leads to reduced expression of the EB-1 and Wnt16b genes; aberrant expression of these genes may be a key step in leukemogenesis in t(1;19)-positive pre-B leukemia. (PMID:16769578)
• Wnt16 does not activate canonical Wnt signaling in E2A-PBX1-positive cells. Instead, beta-catenin is involved in N-cadherin-dependent adherence junctions (PMID:19101069)
• Results demonstrated significant up-regulation of WNT-3, WNT-4, WNT-5B, WNT-7B, WNT-9A, WNT-10A, and WNT-16B in patients with CLL compared to normal subjects. (PMID:19863181)
• study identified WNT16B as a new marker of senescence that regulates p53 activity and the PI3K/AKT pathway and is necessary for the onset of replicative senescence (PMID:19951988)
• these findings postulate that the WNT16/C7orf58 locus contains complex patterns of genetic variation, which play an important role in peak bone mass accrual and may likely impact BMD determination at later life. (PMID:22792070)
• These results suggest a critical role of Wnt 16 signaling pathway on cortical bone thickness and bone strength determination as well as fracture susceptibility. (PMID:22792071)
• Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B. (PMID:22863786)
• Analyses of femoral neck BMD also supported association with SNPs in WNT16 and ESR1/C6orf97 (PMID:23074152)
• Common missense polymorphisms of the WNT16 gene are associated with bone mineral density at the hip, calcaneal ultrasound and the buckling ratio of the femoral neck, as well as with hip fractures in individuals under 80 years of age. (PMID:23417354)
• results suggest synergistic effects of WNT16a insertion and the at-risk ‘T’ allele of TCF7L2 (rs7903146) for elevating the expression of TCF7L2 in human pancreas which may affect the regulation of downstream target genes involved in the development of T2D (PMID:23617586)
• Estrogen/progesterone treatment of mature myometrial cells induced expression of WNT11 and WNT16, which remained constitutively elevated in leiomyoma tissues. (PMID:24082114)
• Increased translation of WNT16 can thus lead to an increased inhibitory action of WNT16 on canonical WNT signaling. (PMID:24185276)
• variants at WNT16 were more strongly related to upper limb-bone mineral density, than to bone mineral density at the other sites. (PMID:24945404)
• Osteoblast-derived WNT16 is a previously unreported key regulator of osteoclastogenesis and fracture susceptibility. (PMID:25306233)
• Describe TGFbeta-Wnt16-Notch signaling conduit in the chondrocyte-like transformation of VSMCs and identify endogenous TGFbeta activity in MGP-null VSMCs as a critical mediator of chondrogenesis. (PMID:25614285)
• MicroRNA-374b Suppresses Proliferation and Promotes Apoptosis in T-cell Lymphoblastic Lymphoma by Repressing AKT1 and Wnt-16 (PMID:26100275)
• ALL cells expressing WNT16 are sensitive to endoplasmic reticulum stress, and show enhanced killing after addition of chloroquine. (PMID:26254351)
• Although in vitro studies demonstrated no differences in expressions of wild-type and mutant forms of IDUA and WNT16B proteins, in silico analyses predicts that WNT16 rs2707466 directly abolishes a phosphorylation site, which could cause a deleterious effect on WNT16 protein. (PMID:26256109)
• ThE findingS suggests that WNT16 might be an important genetic factor in determining peak bone mass acquisition. (PMID:26510844)
• Data indicate that WNT16 is critical for positive regulation of both cortical and trabecular bone mass and structure. WNT16-TG mice exhibited significantly higher whole-body areal bone mineral density and bone mineral content. (PMID:26584014)
• loss of endogenous WNT16 results specifically in cortical bone loss, whereas overexpression of WNT16 surprisingly increases mainly trabecular bone mass. (PMID:26627248)
• PRKX, WNT3 and WNT16 genes, belonging to the WNT signaling pathway, are involved in the tumorigenic process of nodular basal cell carcinoma (PMID:27630294)
• there was a significant difference in the genotypic frequencies of rs2707466 between hypertrophic and atrophic hip OA in males, with overrepresentation of G alleles in the hypertrophic phenotype. An association in the same direction was observed between these alleles and the type of knee OA, with G alleles being more common in the hypertrophic than in atrophic knee phenotypes (PMID:28766055)
• Study identified two rare variants in functional regions of WNT16 (rs190011371 in WNT16b 3’UTR and rs570754792 in the SOST TATA box) found present in women with low BMD. (PMID:30026596)
• significant differences in the polymorphisms of the WNT16 rs2908004 genetic variant contributes to the pathogenesis of osteoporosis (PMID:31309515)
• Short Communication: The Association of WNT16 Polymorphisms with the CD4(+) T Cell Count in the HIV-Infected Population. (PMID:31623455)
• Lower WNT16 expression in patients with adolescent idiopathic scoliosis - potential link to lower bone mass in AIS? (PMID:34190055)
• Associations between WNT signaling pathway-related gene polymorphisms and risks of osteoporosis development in Chinese postmenopausal women: a case-control study. (PMID:34254535)
• Bone mineral density in high-level endurance runners: Part B-genotype-dependent characteristics. (PMID:34550467)
• WNT16 elevation induced cell senescence of osteoblasts in ankylosing spondylitis. (PMID:34879876)
• WNT16 from decidual stromal cells regulates HTR8/SVneo trophoblastic cell function via AKT/beta-catenin pathway. (PMID:35174787)
• Whole-genome sequencing identifies rare missense variants of WNT16 and ERVW-1 causing the systemic lupus erythematosus. (PMID:35283196)
• Genetic Variants in WNT16 and PKD2L1 Locus Affect Heel Ultrasound Bone Stiffness: Analyses from the General Population and Patients Evaluated for Osteoporosis. (PMID:37831088)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	wnt16	ENSDARG00000094973
mus_musculus	Wnt16	ENSMUSG00000029671
rattus_norvegicus	Wnt16	ENSRNOG00000005781
drosophila_melanogaster	Wnt4	FBGN0010453
caenorhabditis_elegans		WBGENE00001188

Paralogs (18): WNT8A (ENSG00000061492), WNT8B (ENSG00000075290), WNT11 (ENSG00000085741), WNT2 (ENSG00000105989), WNT3 (ENSG00000108379), WNT5B (ENSG00000111186), WNT5A (ENSG00000114251), WNT6 (ENSG00000115596), WNT1 (ENSG00000125084), WNT2B (ENSG00000134245), WNT10A (ENSG00000135925), WNT9A (ENSG00000143816), WNT3A (ENSG00000154342), WNT7A (ENSG00000154764), WNT9B (ENSG00000158955), WNT4 (ENSG00000162552), WNT10B (ENSG00000169884), WNT7B (ENSG00000188064)

Protein

Protein identifiers

Protein Wnt-16 — Q9UBV4 (reviewed: Q9UBV4)

All UniProt accessions (2): Q9UBV4, E9PH60

UniProt curated annotations — full annotation on UniProt →

Function. Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Isoform Wnt-16b is expressed in peripheral lymphoid organs such as spleen, appendix, and lymph nodes, in kidney but not in bone marrow. Isoform Wnt-16a is expressed at significant levels only in the pancreas.

Post-translational modifications. Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.

Similarity. Belongs to the Wnt family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UBV4-1	Wnt-16b	yes
Q9UBV4-2	Wnt-16a

RefSeq proteins (2): NP_057171, NP_476509* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005817	Wnt	Family
IPR013304	Wnt16	Family
IPR018161	Wnt_CS	Conserved_site
IPR043158	Wnt_C	Homologous_superfamily

Pfam: PF00110

UniProt features (21 total): disulfide bond 11, sequence variant 3, glycosylation site 3, signal peptide 1, chain 1, splice variant 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBV4-F1	88.67	0.69

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 227

Disulfide bonds (11): 223–230, 294–325, 310–320, 324–364, 340–355, 342–352, 347–348, 81–92, 139–147, 149–168, 221–235

Glycosylation sites (3): 143, 189, 311

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-3238698	WNT ligand biogenesis and trafficking
R-HSA-373080	Class B/2 (Secretin family receptors)

MSigDB gene sets: 187 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, KEGG_HEDGEHOG_SIGNALING_PATHWAY, GOBP_KERATINOCYTE_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, TATTATA_MIR374, GOBP_NEUROGENESIS, GOBP_CELLULAR_SENESCENCE, GOBP_MORPHOGENESIS_OF_EMBRYONIC_EPITHELIUM, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_MESENCHYMAL_CELL_DIFFERENTIATION, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_EMBRYONIC_CAMERA_TYPE_EYE_MORPHOGENESIS

GO Biological Process (16): optic cup formation involved in camera-type eye development (GO:0003408), positive regulation of gene expression (GO:0010628), Wnt signaling pathway (GO:0016055), neuron differentiation (GO:0030182), keratinocyte differentiation (GO:0030216), keratinocyte proliferation (GO:0043616), cell fate commitment (GO:0045165), positive regulation of JNK cascade (GO:0046330), bone remodeling (GO:0046849), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), canonical Wnt signaling pathway (GO:0060070), cardiac epithelial to mesenchymal transition (GO:0060317), replicative senescence (GO:0090399), oxidative stress-induced premature senescence (GO:0090403), negative regulation of apoptotic signaling pathway (GO:2001234), multicellular organism development (GO:0007275)

GO Molecular Function (3): frizzled binding (GO:0005109), cytokine activity (GO:0005125), signaling receptor binding (GO:0005102)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by WNT	1
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell differentiation	2
cellular anatomical structure	2
optic cup morphogenesis involved in camera-type eye development	1
anatomical structure formation involved in morphogenesis	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
cell surface receptor signaling pathway	1
generation of neurons	1
epidermal cell differentiation	1
skin development	1
epithelial cell proliferation	1
cellular developmental process	1
JNK cascade	1
positive regulation of MAPK cascade	1
regulation of JNK cascade	1
tissue remodeling	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
Wnt signaling pathway	1
epithelial to mesenchymal transition	1
heart morphogenesis	1
cell cycle process	1
cellular response to oxidative stress	1
stress-induced premature senescence	1
negative regulation of signal transduction	1
negative regulation of apoptotic process	1
apoptotic signaling pathway	1
regulation of apoptotic signaling pathway	1
multicellular organismal process	1
anatomical structure development	1
G protein-coupled receptor binding	1
receptor ligand activity	1
protein binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1148 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WNT16	FZD6	O60353	782
WNT16	LRP5	O75197	766
WNT16	CTNNB1	P35222	762
WNT16	FZD4	Q9ULV1	712
WNT16	FZD1	Q9UP38	703
WNT16	CPED1	A4D0V7	702
WNT16	SFRP1	Q8N474	680
WNT16	FZD5	Q13467	670
WNT16	FZD2	Q14332	670
WNT16	DKK1	O94907	663
WNT16	LRP6	O75581	658
WNT16	FZD8	Q9H461	650
WNT16	FZD3	Q9NPG1	647
WNT16	SFRP4	Q6FHJ7	603
WNT16	SOST	Q9BQB4	584

IntAct

22 interactions, top by confidence:

A	B	Type	Score
WNT16	WNT11	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
SH2D3C	TMEM14DP	psi-mi:“MI:0914”(association)	0.350
DCAF4	IGLL5	psi-mi:“MI:0914”(association)	0.350
PTCH1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
LDLRAD1	ZNF316	psi-mi:“MI:0914”(association)	0.350
CA6	QSOX1	psi-mi:“MI:0914”(association)	0.350
PDGFRA	QSOX1	psi-mi:“MI:0914”(association)	0.350
CST9L	QSOX1	psi-mi:“MI:0914”(association)	0.350
WNT10A	MANBA	psi-mi:“MI:0914”(association)	0.350
WNT3A	MANBA	psi-mi:“MI:0914”(association)	0.350
EPHA7	PLOD2	psi-mi:“MI:0914”(association)	0.350
OIT3	WNT10B	psi-mi:“MI:0914”(association)	0.350
LYZL1	MAN2B1	psi-mi:“MI:0914”(association)	0.350
SLURP1	MAN2B1	psi-mi:“MI:0914”(association)	0.350
ARSA	CLGN	psi-mi:“MI:0914”(association)	0.350
CST11	PLXNB2	psi-mi:“MI:0914”(association)	0.350
WNT7A	MGRN1	psi-mi:“MI:0914”(association)	0.350
CELA3A	IGF1R	psi-mi:“MI:0914”(association)	0.350
BCL6	CACNA1A	psi-mi:“MI:0914”(association)	0.350

BioGRID (34): PCBP3 (Affinity Capture-MS), GALNS (Affinity Capture-MS), NR2F2 (Affinity Capture-MS), CANX (Affinity Capture-MS), WNT5A (Affinity Capture-MS), TOR3A (Affinity Capture-MS), WLS (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), N4BP2L2 (Affinity Capture-MS), WNT11 (Affinity Capture-MS), WNT16 (Affinity Capture-MS), WNT16 (Affinity Capture-MS), NR2F2 (Affinity Capture-MS), WNT11 (Affinity Capture-MS), TOR3A (Affinity Capture-MS)

ESM2 similar proteins: A0M8S1, A0M8T2, A1X153, A4D7S0, O00755, P09544, P21552, P22725, P22726, P28465, P87387, Q07DV4, Q07DW8, Q07DX7, Q07DY7, Q07DZ8, Q07E18, Q07E31, Q07E44, Q09YI4, Q09YJ6, Q09YK7, Q09YN1, Q108U2, Q1KYK4, Q1KYK5, Q1KYK6, Q1KYK7, Q1KYK9, Q1KYL1, Q2IBB0, Q2IBB5, Q2IBE2, Q2IBF4, Q2IBG1, Q2QL76, Q2QL85, Q2QL96, Q2QLA5, Q2QLB6

Diamond homologs: A0M8S1, A0M8T2, A1X153, A4D7S0, B2GUT4, O00755, O13267, O15978, O42122, O70283, P04426, P04628, P09544, P09615, P10108, P17553, P21551, P21552, P22724, P22725, P22726, P22727, P24257, P24383, P27467, P28047, P28465, P31285, P31286, P33945, P34888, P34889, P41221, P43446, P47793, P49337, P49338, P49339, P49340, P49893

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
WNT16	up-regulates	FZD3	binding
WNT16	up-regulates	LRP6	binding
WNT16	up-regulates	CHRNA1
hsa-miR-374b-5p	“down-regulates quantity by repression”	WNT16	“post transcriptional regulation”
SOSTDC1	“down-regulates activity”	WNT16

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
WNT ligand biogenesis and trafficking	5	105.7×	3e-08
Class B/2 (Secretin family receptors)	6	57.1×	3e-08

GO biological processes:

GO term	Partners	Fold	FDR
cell fate commitment	5	44.8×	3e-05
canonical Wnt signaling pathway	5	23.2×	3e-04
neuron differentiation	5	15.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

58 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

722 predictions. Top by Δscore:

Variant	Effect	Δscore
7:121329815:GCG:G	donor_gain	1.0000
7:121329127:G:GT	donor_gain	0.9900
7:121329127:G:T	donor_gain	0.9900
7:121329181:G:GT	donor_gain	0.9900
7:121329384:GGAT:G	donor_gain	0.9900
7:121329385:GATG:G	donor_gain	0.9900
7:121329388:G:GG	donor_gain	0.9900
7:121329808:C:G	donor_gain	0.9900
7:121329816:CGGTG:C	donor_loss	0.9900
7:121329817:GGT:G	donor_loss	0.9900
7:121329818:G:GA	donor_loss	0.9900
7:121329818:G:GG	donor_gain	0.9900
7:121329819:TGA:T	donor_loss	0.9900
7:121329820:GAGTC:G	donor_loss	0.9900
7:121331676:A:AG	acceptor_gain	0.9900
7:121331677:G:GG	acceptor_gain	0.9900
7:121338880:GGCT:G	acceptor_gain	0.9900
7:121329070:G:GT	donor_gain	0.9800
7:121329166:GTT:G	donor_gain	0.9800
7:121329167:T:TA	donor_gain	0.9800
7:121329178:G:GT	donor_gain	0.9800
7:121329385:GAT:G	donor_gain	0.9800
7:121329561:TTACA:T	acceptor_loss	0.9800
7:121329562:TACA:T	acceptor_loss	0.9800
7:121329564:C:G	acceptor_loss	0.9800
7:121329565:AGGT:A	acceptor_gain	0.9800
7:121329566:G:A	acceptor_loss	0.9800
7:121329566:GGTG:G	acceptor_gain	0.9800
7:121331672:TTCTA:T	acceptor_loss	0.9800
7:121331673:TCTA:T	acceptor_loss	0.9800

AlphaMissense

2413 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:121329741:G:C	W90C	1.000
7:121329741:G:T	W90C	1.000
7:121338914:T:A	C223S	1.000
7:121338915:G:C	C223S	1.000
7:121339175:T:A	C310S	1.000
7:121339176:G:C	C310S	1.000
7:121339271:T:A	C342S	1.000
7:121339272:G:C	C342S	1.000
7:121339277:T:C	F344L	1.000
7:121339278:T:C	F344S	1.000
7:121339278:T:G	F344C	1.000
7:121339279:C:A	F344L	1.000
7:121339279:C:G	F344L	1.000
7:121331693:C:A	A121E	0.999
7:121331746:T:A	C139S	0.999
7:121331747:G:A	C139Y	0.999
7:121331747:G:C	C139S	0.999
7:121331748:C:G	C139W	0.999
7:121331826:G:C	W165C	0.999
7:121331826:G:T	W165C	0.999
7:121331833:T:A	C168S	0.999
7:121331834:G:C	C168S	0.999
7:121331866:A:C	S179R	0.999
7:121331868:C:A	S179R	0.999
7:121331868:C:G	S179R	0.999
7:121338908:T:A	C221S	0.999
7:121338909:G:C	C221S	0.999
7:121338914:T:C	C223R	0.999
7:121338917:C:G	H224D	0.999
7:121338921:G:A	G225E	0.999

dbSNP variants (sampled 300 via entrez): RS1000064365 (7:121329914 A>G), RS1000300224 (7:121323968 C>T), RS1000461599 (7:121323683 G>A), RS1000891167 (7:121326003 C>G,T), RS1000948900 (7:121332363 C>A,T), RS1001173182 (7:121326394 T>C), RS1001420597 (7:121338851 A>C), RS1001720377 (7:121339732 G>A), RS1001845791 (7:121323754 G>A), RS1002055896 (7:121341518 C>A,G), RS1002150792 (7:121341163 A>G), RS1002332813 (7:121334572 C>A), RS1002724951 (7:121338302 T>C,G), RS1002998836 (7:121331501 C>A,T), RS1003090437 (7:121325735 T>C)

Disease associations

OMIM: gene MIM:606267 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

51 associations (top):

Study	Trait	p-value
GCST001482_20	Lumbar spine bone mineral density	3.000000e-51
GCST001593_2	Cortical thickness	2.000000e-10
GCST001594_1	Bone mineral density	1.000000e-27
GCST001595_1	Bone mineral density	1.000000e-15
GCST002276_5	Bone mineral density	2.000000e-10
GCST002333_4	Bone properties (heel)	2.000000e-59
GCST002334_2	Bone properties (heel)	1.000000e-09
GCST002335_4	Bone properties (heel)	4.000000e-35
GCST002492_1	Bone mineral density (paediatric, lower limb)	3.000000e-11
GCST002492_10	Bone mineral density (paediatric, lower limb)	1.000000e-09
GCST002493_15	Bone mineral density (paediatric, skull)	3.000000e-22
GCST002493_16	Bone mineral density (paediatric, skull)	2.000000e-28
GCST002494_15	Bone mineral density (paediatric, total body less head)	2.000000e-15
GCST002494_3	Bone mineral density (paediatric, total body less head)	6.000000e-20
GCST002496_11	Bone mineral density (paediatric, upper limb)	1.000000e-37
GCST002496_7	Bone mineral density (paediatric, upper limb)	3.000000e-32
GCST002952_3	Pediatric bone mineral content (radius)	3.000000e-08
GCST003611_3	Bone mineral density (total hip)	9.000000e-09
GCST003611_4	Bone mineral density (total hip)	4.000000e-08
GCST003612_3	Bone mineral density (femoral neck)	1.000000e-06
GCST003612_4	Bone mineral density (femoral neck)	6.000000e-07
GCST004350_11	Bone ultrasound measurement (velocity of sound)	2.000000e-48
GCST004350_13	Bone ultrasound measurement (velocity of sound)	2.000000e-29
GCST004350_3	Bone ultrasound measurement (velocity of sound)	1.000000e-21
GCST004351_16	Bone ultrasound measurement (broadband ultrasound attenuation)	1.000000e-51
GCST004351_4	Bone ultrasound measurement (broadband ultrasound attenuation)	1.000000e-27
GCST004351_7	Bone ultrasound measurement (broadband ultrasound attenuation)	4.000000e-27
GCST004771_6	TB-LM or TBLH-BMD (pleiotropy)	3.000000e-20
GCST004772_6	Bone mineral density (paediatric, total body less head)	5.000000e-17
GCST005546_1	Forearm bone mineral density	1.000000e-25

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004840	cortical thickness
EFO:0005654	velocity of sound measurement
EFO:0004514	bone quantitative ultrasound measurement
EFO:0007621	bone mineral content measurement
EFO:0007702	hip bone mineral density
EFO:0007785	femoral neck bone mineral density
EFO:0004995	lean body mass
EFO:0007933	radius bone mineral density
EFO:0007701	spine bone mineral density
EFO:0009270	heel bone mineral density
EFO:0001425	ischemic cardiomyopathy
EFO:0009936	Drugs affecting bone structure and mineralization use measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Copper	affects binding, decreases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
arsenite	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
theaflavin-3,3’-digallate	affects expression	1
Irinotecan	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic Trioxide	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Chelating Agents	affects binding, decreases expression	1
Estradiol	decreases expression, affects cotreatment	1
Methotrexate	increases expression	1
Progesterone	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Dronabinol	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Okadaic Acid	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8Y6	Ubigene HCT 116 WNT16 KO	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.